X-Ray irradiation induced changes of the nuclear membrane of Kirkman-Robbins tumour cells

Djaczenko, W.; Starzyk, H.; Rzucidło, Z.

doi:10.1007/bf01913267

Cited by 5 publications

(7 citation statements)

References 2 publications

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“…However, physiologically extreme conditions, including contraction of muscular cells, depolymerization during cell division, the exposition to ionizing radiation, and genetic mutations, can lead to flaws and defects within the meshwork structure. Accumulated flaws can result in the generation of crack-like defects as shown in earlier experimental work [9].…”

Section: Introductionmentioning

confidence: 92%

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Dynamic Failure of a Lamina Meshwork in Cell Nuclei under Extreme Mechanical Deformation

Qin

Buehler

2011

BioNanoSci.

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The nuclear lamina is a structural protein meshwork at the inner nuclear membrane. It confers mechanical strength to the cell's nucleus and also sustains the overall structural integrity of the cell. The rupture of nuclear lamina is involved in many physiologically extreme conditions, such as cell division, genetic disease, and injury. Yet, its rupture mechanisms and processes are largely unknown and failure models commonly used for engineering materials cannot be directly applied due to the complex hierarchical structure. Here, we use a multiscale modeling technique to investigate the dynamic failure of the nuclear lamina meshwork from the bottom up. We find that flaws or cracks in the nuclear lamina act as seeds for catastrophic failure that propagate rapidly upon very large deformation. Fracture occurs via crack propagation at intersonic speeds, and greater than the Rayleigh-wave speed predicted as a limit by classical fracture theory but smaller than the longitudinal wave speed. Our analysis shows that nanoscale secondary structural changes in protein filaments such as the alpha-beta transition and intermolecular sliding explain this macroscale phenomenon. Based on a simple model, we discover that the crack propagation speed is governed by the square root of the ratio of the tangent material moduli in (E x ) and perpendicular (E y ) to the crack propagationwhere the relative levels of applied strains in the x-and y-direction control the crack speed.

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Section: Introductionmentioning

confidence: 92%

“…1b includes 20 filaments in the y-direction (1 μm) and 100 filaments (5 μm) in the x-direction, with a crack-like defect added in the center to mimic a structural imperfection [9]. Filaments at the orthogonal corners are cross-linked by strong, covalent bonds which cannot break apart in our model.…”

Section: Simulation Setupmentioning

confidence: 99%

Dynamic Failure of a Lamina Meshwork in Cell Nuclei under Extreme Mechanical Deformation

Qin

Buehler

2011

BioNanoSci.

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“…28 Although there is some experimental evidence that nuclear pore complexes act like rivets, 28 there is also evidence that rupture and breakdown of nuclear envelopes tend to occur around nuclear pore complexes. 17 The improvement of defect modeling of nuclear pore complexes requires more information of the interaction between the complex and nuclear lamina and has yet to be established.…”

Section: Articlementioning

confidence: 99%

“…13,14,16 Other possible factors include ionizing radiation that results in the breakage of covalent or noncovalent bonds within protein structures and thus results in structural defects. [17][18][19] It has been shown that continuous radiation, as experienced for example during space flight, causes cracks to occur around nuclear pores which leads to a complete fragmentation of nuclear envelopes once a critical defect concentration is reached 17 (see Figure S2 in the Supporting Information). While experimental data has provided clear evidence that nuclei in healthy cells can effectively withstand extreme dilations and deformation without rupture, 15 conventional material models have failed to explain their significant capacity to expand without failure.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Flaw Tolerance of Nuclear Intermediate Filament Lamina under Extreme Mechanical Deformation

Qin

Buehler²

2011

ACS Nano

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The nuclear lamina, composed of intermediate filaments, is a structural protein meshwork at the nuclear membrane that protects genetic material and regulates gene expression.Here we uncover the physical basis of the material design of nuclear lamina that enables it to withstand extreme mechanical deformation of >100% strain despite the presence of structural defects. Through a simple in silico model we demonstrate that this is due to nanoscale mechanisms including protein unfolding, alpha-to-beta transition, and sliding, resulting in a characteristic nonlinear force-extension curve. At the larger microscale this leads to an extreme delocalization of mechanical energy dissipation, preventing catastrophic crack propagation. Yet, when catastrophic failure occurs under extreme loading, individual protein filaments are sacrificed rather than the entire meshwork. This mechanism is theoretically explained by a characteristic change of the tangent stress-strain hardening exponent under increasing strain. Our results elucidate the large extensibility of the nuclear lamina within muscle or skin tissue and potentially many other protein materials that are exposed to extreme mechanical conditions, and provide a new paradigm toward the de novo design of protein materials by engineering the nonlinear stress-strain response to facilitate flaw-tolerant behavior.

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Radiation response of cell organelles

Somosy

2000

Micron

169

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X-Ray irradiation induced changes of the nuclear membrane of Kirkman-Robbins tumour cells

Cited by 5 publications

References 2 publications

Dynamic Failure of a Lamina Meshwork in Cell Nuclei under Extreme Mechanical Deformation

Dynamic Failure of a Lamina Meshwork in Cell Nuclei under Extreme Mechanical Deformation

Flaw Tolerance of Nuclear Intermediate Filament Lamina under Extreme Mechanical Deformation

Radiation response of cell organelles

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